Procedures for determining the presence or absence of specific organisms or viruses in a test sample commonly rely upon nucleic acid-based probe testing. To increase the sensitivity of these tests, an amplification step is often included to increase the number of potential nucleic acid target sequences present in the test sample. There are many amplification procedures in common use today, including the polymerase chain reaction (PCR), Q-beta replicase, self-sustained sequence replication (3SR), transcription-mediated amplification (TMA), nucleic acid sequence-based amplification (NASBA), ligase chain reaction (LCR), strand displacement amplification (SDA) and loop-mediated isothermal amplification (LAMP), each of which is well known in the art. See, e.g., Mullis, “Process for Amplifying Nucleic Acid Sequences,” U.S. Pat. No. 4,683,202; Erlich et al., “Kits for Amplifying and Detecting Nucleic Acid Sequences,” U.S. Pat. No. 6,197,563; Walker et al., Nucleic Acids Res., 20:1691-1696 (1992); Fahy et al., “Self-sustained Sequence Replication (3SR): An Isothermal Transcription-Based Amplification System Alternative to PCR,” PCR Methods and Applications, 1:25-33 (1991); Kacian et al., “Nucleic Acid Sequence Amplification Methods,” U.S. Pat. No. 5,399,491; Davey et al., “Nucleic Acid Amplification Process,” U.S. Pat. No. 5,554,517; Birkenmeyer et al., “Amplification of Target Nucleic Acids Using Gap Filling Ligase Chain Reaction,” U.S. Pat. No. 5,427,930; Marshall et al., “Amplification of RNA Sequences Using the Ligase Chain Reaction,” U.S. Pat. No. 5,686,272; Walker, “Strand Displacement Amplification,” U.S. Pat. No. 5,712,124; Notomi et al., “Process for Synthesizing Nucleic Acid,” U.S. Pat. No. 6,410,278; Dattagupta et al., “Isothermal Strand Displacement Amplification,” U.S. Pat. No. 6,214,587; and HELEN H. LEE ET AL., NUCLEIC ACID AMPLIFICATION TECHNOLOGIES: APPLICATION TO DISEASE DIAGNOSIS (1997).
A concern with amplification is the possibility of cross-contamination, since transferring even a minute amount of target-containing sample to a target-negative sample could lead to the production of billions of target sequences in the “negative” sample. As a consequence, a test may indicate a positive result for a sample actually lacking nucleic acid from an organism or virus of interest. The source of a contaminating sample transfer may be an aerosol or bubbles released from a sample tube when a cap component of the sample tube is removed or penetrated by a practitioner or instrument. To minimize such sources of contamination, collection devices which include penetrable caps having filtering means have been introduced for use with automated analyzers. Such collection devices include the APTIMA® Urine Specimen Collection Kit for Male and Female Urine Specimens (Gen-Probe Incorporated, San Diego, Calif.; Cat. No. 1040), which is an embodiment of the collection devices disclosed by Kacian et al., “Penetrable Cap,” U.S. Pat. No. 6,893,612.
The components of a penetrable cap generally exert a retention force against a fluid transfer device (e.g., pipette tip) as the fluid transfer device is being withdrawn from an associated sample tube. See, e.g., Ammann et al., “Automated Process for Isolating and Amplifying a Target Nucleic Acid Sequence,” U.S. Pat. No. 6,335,166 (an instrument for performing amplification assays on test samples which includes a robotic pipettor using disposable pipette tips for obtaining test sample from a sample tube is disclosed). The retention force may be attributable to, for example, the sealing material of the cap and/or filtering means included within the cap exerting a frictional force on the fluid transfer device. The retention force may also be caused by a swab used for specimen collection (e.g., a cervical, urethral or urinary tract specimen) which is angled in the sample tube or where multiple swabs have been inadvertently inserted into the same sample tube. Swabs used for specimen collection may be provided with a mid-section score line for snapping off the upper portion of the swab. (Such swabs are described by Pestes et al., “Cell Collection Swab,” U.S. Pat. No. 5,623,942, and one such commercial product is the APTIMA® Unisex Swab Specimen Collection Kit for Endocervical and Male Urethral Swab Specimens, available from Gen-Probe as Cat. No. 1041.) If properly broken, the remainder of the swab should fit along the inner wall of the sample tube below the cap. But, if the snap occurs above the score line, then when the swab is fitted into the sample tube, and the cap is screwed onto the sample tube, the swab may bow in such a way that it interferes with the path of a pipette tip inserted through the cap.
If the retention force is too great, attempts to remove the fluid transfer device from the associated sample tube could result in the sample tube being withdrawn from a sample carrier holding the sample tube. In a more extreme case, the retention force of the cap and the sample tube holding force of the sample carrier are each great enough that the sample carrier is lifted vertically as the fluid transfer device is being withdrawn from the sample tube.
Conventional sample carriers commonly rely upon springs to immobilize sample tubes, biasing the sample tubes against one or more opposing surfaces of the sample carriers. And more recently, a sample carrier has been described which further includes a top wall portion having a plurality of openings which are configured and arranged so that penetrable caps affixed to the vessel components of sample tubes are positioned snugly within the openings when the sample tubes are held by the sample carrier, thereby centering the sample tubes by restricting lateral movement of the corresponding caps within the openings. See Sevigny et al., “Sample Carrier and Drip Shield for Use Therewith,” U.S. Pat. Application Publication No. US 2003-0215365 A1. Furthermore, the sample carriers described include a mechanism, such as a sample tube blocking member, for ensuring that sample tubes remain in the sample carriers during automated sampling procedures when the retention force generated by a cap onto a portion of the fluid transfer device (e.g., pipette tips) is greater than the holding force of the sample carrier on an associated sample tube component.
Furthermore, a drip shield has been described for use in an automated sampling system to protect the contents of sample tubes held by sample carriers from fluid contamination, especially hanging droplets which may be dislodged from a robotic pipetting device during an automated sampling procedure. See Sevigny et al., “Sample Carrier and Drip Shield for Use Therewith,” U.S. Patent Application Publication No. US 2003-0215365 A1. By “automated sampling system” is meant a system for holding a sample tube in a generally upright orientation and conveying the sample tube by automated means (e.g., a transport mechanism) to a location within an apparatus where the contents of the sample tube may be accessed by an automated substance transfer mechanism, such as a robotic pipetting device, in order to effect a transfer of at least a portion of the contents to another location within the apparatus. The drip shield includes a cover member having one or more access holes, where each access hole is configured and arranged to provide non-interfering, vertical passage of an aligned pipette tip therethrough. The access holes are sized to permit access to the contents of only one sample tube at a time, where the sample tubes being accessed are present in a sample carrier positioned beneath the cover member. The diameter of each access hole is preferably the same as or smaller than the smallest diameter of any sample tube cap associated with a sample tube held by the sample carrier to minimize opportunities for contaminating the sample carrier and its contents.
A potential problem associated with the above-described sample carrier and drip shield configurations occurs when a disposable pipette tip is dislodged from a pipette tip mounting shaft of a robotic pipetting device while the pipette tip is inserted through an access hole in the drip shield and into the sample tube. The pipette tip can, for example, become unseated or dislodged when the frictional retention force created by the sample tube cap or a specimen collection swab (as described above) on the pipette tip, as the pipette tip is being withdrawn from the cap, exceeds the force required to dislodge the pipette tip from the pipette tip mounting shaft. When a pipette tip becomes dislodged and extends upward through an access hole of the drip shield, the sample carrier is prevented from advancing beneath the drip shield. To correct this problem, an operator must terminate operation of the apparatus, reach into the apparatus and remove the dislodged pipette tip or push the pipette tip far enough into the sample tube to clear the drip shield. This corrective procedure can be awkward and inconvenient—if not altogether impossible—if the sample transfer location is in a difficult to access location within the apparatus. Ideally, sample carriers could be conveyed away from the drip shield on a lateral transport path to a location where the operator could more easily reach and remove the dislodged pipette tip.
Accordingly, a need exists for a drip shield design that will allow the sample carrier to be conveyed laterally away from the drip shield when a dislodged pipette tip extends through an access hole of the drip shield, while still maintaining protection of the sample tubes being conveyed beneath the drip shield.